CUSHING'S SYNDROME WITH BILATERAL MULTINODULAR ADRENAL HYPERPLASIA

An unusual case of Cushing's syndrome of a 59-year-old man with bilateral multinodular adrenal hyperplasia and microadenoma of the pituitary gland is presented. Failure to suppress plasma Cortisol with large doses of dexamethasone may suggest autonomous growth of hyperplastic nodules of the adrenals, which were at first induced by prolonged stimuli of ACTH from the microadenoma of the pituitary gland. ACTH could not be detected in the microadenoma cells on paraffin sections, while Crooke's cells were strongly positive for ACTH. The interrelation between bilateral multinodular adrenal hyperplasia and pituitary microadenoma is discussed.     

Analysis of mRNA with microsomal fractionation using a SAGE-based DNA microarray system facilitates identification of the genes encoding secretory proteins

In the regulation of host defense responses such as inflammation and immunity, the secretory proteins, including membrane proteins, play central roles. Although many secretory proteins have been identified by using methods such as differential display, random screening, or the signal sequence trap method, each method suffers from poor reproducibility, low sensitivity, or time-consuming or laborious work. Therefore, the strategy for facilitating the selection of the genes encoding the secretory proteins is desired. In this paper, we describe a system for isolating the genes encoding secretory proteins by analyzing mRNAs with microsomal fractionation on serial analysis of gene expression (SAGE)-based DNA microarray system. This system succeeded in discriminating the genes encoding secretory proteins from ones encoding nonsecretory proteins with 80% accuracy. We applied this system to human T lymphocytes. As a result, we were able to identify the genes that are not only encoding secretory proteins but also expressing selectively in a specific subset of T lymphocytes. The SAGE-based DNA microarray system is a promising system to identify the genes encoding specific secretory proteins.     

Prevalence of chlamydia-pneumoniae-specific immunoglobulin M antibody and acute exacerbations of asthma in childhood]

BACKGROUND: Chlamydia pneumoniae is a frequent causative agent of acute respiratory disease and has been recently reported as a possible cause of asthma. We investigated the prevalence of C. pneumoniae infections in childhood patients with acute exacerbations of asthma. METHOD: One hundred twenty-six childhood patients with acute exacerbations of asthma, 77 with acute bronchitis and 22 Respiratory syncytial virus infections were studied. Serum samples were obtained and tested for C. pneumoniae-specific IgM antibody by Enzyme-Linked ImmunoSorbent Assay (ELISA). RESULTS: C. pneumoniae IgM-positive results were observed in 48.4% (Index value>or=1.60) and 23% (Index value>or=1.10) of patients with acute exacerbations of asthma. The prevalence of C. pneumoniae-specific IgM was significantly higher in asthma cases than in other subjects (p<0.05). CONCLUSION: Our data suggest that C. pneumoniae infection may trigger acute exacerbations of childhood asthma.     

HISTOPATHOLOGICAL STUDIES ON THROMBOTIC MICROANGIOPATHY WITH SPECIAL REFERENCES TO THREE CASES ASSOCIATED WITH ACUTE PROMYELOCYTIC LEUKAEMIA

Five autopsy cases of thrombotic microangiopathy, including 3 cases associated with acute promyelocytic leukaemia, were examined macroscopically, light-and electronmicroscopically.
The so-called hyaline thrombi In thrombotic microangiopathy were composed of fibrin and its degenerative products. Thrombocytes and other blood cells were not seen in the thrombi.
At the site of the formation of a thrombus, there was no conspicuous change in the walls of the capillaries and arterioles. It was considered, therefore, that the intravascular deposition of fibrin was the primary event in the development of thrombotic microangiopathy.
In regard to the distribution and morphologic findings, there was no basic difference between the microthrombi in cases associated with acute promyelocytic leukaemia and those without it.
The bone marrow and some other organs in cases of thrombotic microangiopathy associated with acute promyelocytic leukaemia macroscopically revealed a green colour. Many thrombi composed of leukaemic cells and fibrin were found in the pulmonary arteries of these cases. Furthermore, prominent erythrophagocytosis in the bone marrow and lymph nodes was a common finding in these cases.     

Comparative studies with various substrains of Mycobacterium bovis BCG on the production of an antigenic protein, MPB70.

A protein, isolated and purified from the unheated culture filtrate of Mycobacterium bovis BCG (substrain Tokyo 172) and designated MPB70, elicited a delayed skin reaction in guinea pigs sensitized with viable cells of BCG but not in those sensitized with heat-killed cells. The skin reaction reached the maximum 4 to 8 weeks after the inoculation of the BCG and then decreased gradually, resulting in conversion to negative after 20 weeks, whereas the skin reaction to purified protein derivative (PPD) continued to be positive. Guinea pigs immunized with viable cells of various substrains of BCG were skin tested with MPB70 and PPD. Guinea pigs immunized with the BCG substrain Tokyo 172 and the substrain Moreau (Brazil) showed strong delayed skin reactions to both MPB70 and PPD. On the other hand, guinea pigs immunized with the Pasteur substrain 1173P2, the Glaxo substrain 1077, the Copenhagen substrain 1331, the Tice substrain, or the Beijing substrain 64-42 showed negative skin reactions to MPB70, whereas they were strongly positive to PPD. In a two-dimensional acrylamide gel electrophoretic analysis of proteins from the culture filtrates of the BCG substrains, the culture filtrates of the Tokyo and Moreau substrains showed the spot of MPB70 on the gel slabs, whereas those of the other BCG substrains did not.     

Activation of precursors to both glycoproteins of Newcastle disease virus by proteolytic cleavage

With strain Ulster of Newcastle disease virus, two precursor glycoproteins, HN₀ and F₀, were identified; these are converted by proteolytic cleavage into glycoproteins HN and F, respectively. Purified virions containing predominantly glycoproteins HN₀ and F₀ together with a small amount of HN are not hemolytic and have reduced levels of hemagglutinating and neuraminidase activity and of infectivity. After in vitro treatment with the appropriate proteolytic enzymes, biological activities are fully expressed in these particles. The precursor glycoprotein HN₀ was isolated and found to be largely devoid of hemagglutinating and neuraminidase activities. High levels of both activities were present, however, when this material was subjected to proteolytic cleavage. These observations demonstrate that cleavage is a precondition for the biological activity not only of glycoprotein F but also of glycoprotein HN. There is a striking difference between glycoproteins HN₀ and F₀ with repsect to their susceptibility to proteolytic enzymes. Cleavage and activation of HN₀ can be accomplished by a variety of proteases, such as chymotrypsin, elastase, thermolysin, and trypsin. In contrast, F₀ shows a specific requirement for trypsin.     

Three antigenic variant groups in human respiratory syncytial virus subgroup B isolated in Japan

Summary Nineteen hybridomas producing monoclonal antibodies (MAbs) against the structural proteins of strain 58–17, a subgroup B field strain of respiratory syncytial virus (RSV) isolated in Japan, were obtained by fusion of X 63 myeloma cells with spleen cells from BALB/c mice immunized with the virus-infected HEp-2 cells. Seven clones were found to produce antibodies against the fusion protein (F), five against the large glycoprotein (G), five against the nucleoprotein (NP) and two against the 22k protein by radioimmunoprecipitation assay. By competitive binding assay with the MAbs, at least seven, two, three and one epitopes were defined on the F, G, NP and 22k protein components of subgroup B strain, respectively. Of these epitopes, three, two and one epitopes on the F, G and NP components were different from subgroup A strain, respectively. Fifty-three other field strains of subgroup B isolated in Sapporo, Japan, during nine epidemic years from 1980 to 1989, were examined for reactivity with the MAbs by ELISA. Different reactivity to one anti-NP antibody suggested that the 53 strains can be divided into three groups (B-a: 26 strains, B-b: 26 strains, and one other strain). The dominant strain prevailing during the 1984 to 1988 epidemic years had changed from B-a to B-b. All of the 53 subgroup B strains reacted similarly with the other 18 MAbs.     

Quantitative Analysis of Mycobacterial and Propionibacterial DNA in Lymph Nodes of Japanese and European Patients with Sarcoidosis

The cause(s) of sarcoidosis is unknown. Mycobacterium spp. are suspected in Europe and Propionibacterium spp. are suspected in Japan. The present international collaboration evaluated the possible etiological links between sarcoidosis and the suspected bacterial species. Formalin-fixed and paraffin-embedded sections of biopsy samples of lymph nodes, one from each of 108 patients with sarcoidosis and 65 patients with tuberculosis, together with 86 control samples, were collected from two institutes in Japan and three institutes in Italy, Germany, and England. Genomes of Propionibacterium acnes, Propionibacterium granulosum, Mycobacterium tuberculosis, Mycobacterium avium subsp. paratuberculosis, and Escherichia coli (as the control) were counted by quantitative real-time PCR. Either P. acnes or P. granulosum was found in all but two of the sarcoid samples. M. avium subsp. paratuberculosis was found in no sarcoid sample. M. tuberculosis was found in 0 to 9% of the sarcoid samples but in 65 to 100% of the tuberculosis samples. In sarcoid lymph nodes, the total numbers of genomes of P. acnes or P. granulosum were far more than those of M. tuberculosis. P. acnes or P. granulosum was found in 0 to 60% of the tuberculosis and control samples, but the total numbers of genomes of P. acnes or P. granulosum in such samples were less than those in sarcoid samples. Propionibacterium spp. are more likely than Mycobacteria spp. to be involved in the etiology of sarcoidosis, not only in Japanese but also in European patients with sarcoidosis.